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GeneBe

2-169305709-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004525.3(LRP2):c.427+1572C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,154 control chromosomes in the GnomAD database, including 3,302 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3302 hom., cov: 32)

Consequence

LRP2
NM_004525.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.588
Variant links:
Genes affected
LRP2 (HGNC:6694): (LDL receptor related protein 2) The protein encoded by this gene, low density lipoprotein-related protein 2 (LRP2) or megalin, is a multi-ligand endocytic receptor that is expressed in many different tissues but primarily in absorptive epithilial tissues such as the kidney. This glycoprotein has a large amino-terminal extracellular domain, a single transmembrane domain, and a short carboxy-terminal cytoplasmic tail. The extracellular ligand-binding-domains bind diverse macromolecules including albumin, apolipoproteins B and E, and lipoprotein lipase. The LRP2 protein is critical for the reuptake of numerous ligands, including lipoproteins, sterols, vitamin-binding proteins, and hormones. This protein also has a role in cell-signaling; extracellular ligands include parathyroid horomones and the morphogen sonic hedgehog while cytosolic ligands include MAP kinase scaffold proteins and JNK interacting proteins. Recycling of this membrane receptor is regulated by phosphorylation of its cytoplasmic domain. Mutations in this gene cause Donnai-Barrow syndrome (DBS) and facio-oculoacoustico-renal syndrome (FOAR).[provided by RefSeq, Aug 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRP2NM_004525.3 linkuse as main transcriptc.427+1572C>G intron_variant ENST00000649046.1
LRP2XM_011511183.4 linkuse as main transcriptc.427+1572C>G intron_variant
LRP2XM_047444340.1 linkuse as main transcriptc.-498+1572C>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRP2ENST00000649046.1 linkuse as main transcriptc.427+1572C>G intron_variant NM_004525.3 P1
LRP2ENST00000443831.1 linkuse as main transcriptc.427+1572C>G intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.205
AC:
31097
AN:
152036
Hom.:
3300
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.238
Gnomad AMI
AF:
0.0450
Gnomad AMR
AF:
0.166
Gnomad ASJ
AF:
0.235
Gnomad EAS
AF:
0.0764
Gnomad SAS
AF:
0.185
Gnomad FIN
AF:
0.240
Gnomad MID
AF:
0.196
Gnomad NFE
AF:
0.199
Gnomad OTH
AF:
0.212
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.204
AC:
31111
AN:
152154
Hom.:
3302
Cov.:
32
AF XY:
0.205
AC XY:
15283
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.238
Gnomad4 AMR
AF:
0.166
Gnomad4 ASJ
AF:
0.235
Gnomad4 EAS
AF:
0.0764
Gnomad4 SAS
AF:
0.184
Gnomad4 FIN
AF:
0.240
Gnomad4 NFE
AF:
0.199
Gnomad4 OTH
AF:
0.211
Alfa
AF:
0.205
Hom.:
424
Bravo
AF:
0.198
Asia WGS
AF:
0.123
AC:
428
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
Cadd
Benign
0.36
Dann
Benign
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs830971; hg19: chr2-170162219; API